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Metabolism of the carcinogen chromate by cellular constituents

  • Paul H. Connett
  • Karen E. Wetterhahn
Conference paper
Part of the Structure and Bonding book series (STRUCTURE, volume 54)

Abstract

The redox chemistry of chromium(VI) is discussed with respect to the cellular metabolism of the carcinogen chromate in vivo. Possible sites for cellular reduction of chromium(VI) to chromium(III) are considered. The reactions of amino acids, ascorbic acid, carboxylic acids, thiol-containing mole-cules and other small molecules with chromate under physiological conditions are presented. In general only ascorbate and those molecules containing sulfhydryl groups are capable of easily reducing chromate at pH 7.4. Thus, in the cytoplasm, glutathione, cysteine and ascorbate are likely candidates to react with chromate. While most proteins are unreactive toward chromate, certain redox proteins are active in reducing chromate. The heme proteins hemoglobin and cytochrome P-450 possess chromate-reductase activity, whereas cytochrome c and myoglobin are inactive. The NADPH-dependent flavoenzymes glutathione reductase and NADPH-cytochrome P-450 reductase also possess chromate-reductase activity. However, the NAD(P)H enzymes, isocitrate dehydrogenase, glutamate dehyrogenase and malate dehydrogenase do not reduce chromate. Both microsomes and mitochondria possess chromate-reductase activity. The microsomal activity is accounted for by the NADPH-cytochrome P-450 reductase/cytochrome P-450 system. The enzyme(s) responsible for the mitochondrial reduction of chromate have not been identified. Chromium(VI) and its metabolite chromium(III) inhibit the normal activities of enzymes which bind chromium(III) or reduce chromate. The metabolism of chromate involves the generation of reactive intermediates which ultimately bind to cellular constituents and damage their function in the cell.

Keywords

Lipoic Acid Order Rate Constant Cellular Constituent Chromate Reduction Chromate Reductase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

GSH

glutathione (reduced form)

GSSG

glutathione (oxidized form)

Cys

cysteine

PSH

penicillamine (reduced form)

PSSP

penicillamine (oxidized form)

BAL

2,3-dimercaptopropanol

Unithiol

2,3-dimercapto-1-propane sulfonic acid

DTT

dithiothreitol

NADH

nicotinamide adenine dinucleotide (reduced form)

NAD+

nicotinamide adenine dinucleotide (oxidized form)

NADPH

nicotinamide adenine dinucleotide phosphate (reduced form)

NADP+

nicotinamide adenine dinucleotide phosphate (oxidized form)

RBC

red blood cell

Hb

deoxyhemoglobin

Hb+

methemoglobin

Mb

deoxymyoglobin

Mb+

metmyoglobin

GSSG-R

glutathione reductase

Tris

tris(hydroxymethyl)aminomethane

BP

benzo[a]pyrene

ER

endoplasmic reticulum

mt

mitochondria

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Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Paul H. Connett
    • 1
  • Karen E. Wetterhahn
    • 1
  1. 1.Department of ChemistryDartmouth CollegeHanoverUSA

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